Biology subjects

Khizroev, S.

Publications and source records attributed to Khizroev, S..

3 recordsLinked to original sources

bioRxiv2026

Ultra-high-efficacy Wireless Neuromodulation Using a Conductive Ring Interface

An ab-initio physics study, supported with a COMSOL-based numerical simulation, presents a concept to enable wearable, highly targeted, and ultra-high-efficacy neuromodulation. A target site is defined by a relatively small gap of a miniaturized ring-shaped conductive interface implant. If the implant conductivity significantly exceeds the conductivity of the biological tissue, a highly localized electromotive force (emf) is induced in the ring upon application of an alternating current (AC) magnetic field. This emf generates an electric field in the gap, inducing local neural stimulation of the targeted site, e.g., translated to a nerve segment using circumferential cuffs. The wirelessly controlled autonomous stimulator implant acts as a low-resistance nearly-closed path to generate a highly localized electric field on the order of 50 V/m in the gap via application of a 1-kA/m AC magnetic field at a frequency of 10 kHz. The magnetic field is at least three orders of magnitude smaller than the magnetic field required to generate the same electric field strength via conventional transcranial magnetic stimulation. Therefore, this high-resolution, orientation-specific ring neuromodulation system could enable a highly localized, energy-efficient wearable device with significant preclinical and clinical potential.

bioengineering↗

bioRxiv2024

Nanoparticles use magnetoelectricity to target and eradicate cancer cells

This study presents the first in vivo and in vitro evidence of an externally controlled, predictive, MRI-based nanotheranostic agent capable of cancer cell specific targeting and killing via irreversible electroporation (IRE) in solid tumors. The rectangular-prism-shaped magnetoelectric nanoparticle is a smart nanoparticle that produces a local electric field in response to an externally applied magnetic field. When externally activated, MENPs are preferentially attracted to the highly conductive cancer cell membranes, which occurs in cancer cells because of dysregulated ion flux across their membranes. In a pancreatic adenocarcinoma murine model, MENPs activated by external magnetic fields during magnetic resonance imaging (MRI) resulted in a mean three-fold tumor volume reduction (62.3% vs 188.7%; P < .001) from a single treatment. In a longitudinal confirmatory study, 35% of mice treated with activated MENPs achieved a durable complete response for 14 weeks after one treatment. The degree of tumor volume reduction correlated with a decrease in MRI T2* relaxation time (r = .351; P = .039) which suggests that MENPs have a potential to serve as a predictive nanotheranostic agent at time of treatment. There were no discernable toxicities associated with MENPs at any timepoint or on histopathological analysis of major organs. MENPs are a noninvasive alternative modality for the treatment of cancer. SummaryWe investigated the theranostic capabilities of magnetoelectric nanoparticles (MENPs) combined with MRI via a murine model of pancreatic adenocarcinoma. MENPs leverage the magnetoelectric effect to convert an applied magnetic field into local electric fields, which can induce irreversible electroporation of tumor cell membranes when activated by MRI. Additionally, MENPs modulate MRI relaxivity, which can be used to predict the degree of tumor ablation. Through a pilot study (n=21) and a confirmatory study (n=27), we demonstrated that, [≥]300 {micro}g of MRI-activated MENPs significantly reduced tumor volumes, averaging a three-fold decrease as compared to controls. Furthermore, there was a direct correlation between the reduction in tumor T2 relaxation times and tumor volume reduction, highlighting the predictive prognostic value of MENPs. Six of 17 mice in the confirmatory studys experimental arms achieved a durable complete response, showcasing the potential for durable treatment outcomes. Importantly, the administration of MENPs was not associated with any evident toxicities. This study presents the first in vivo evidence of an externally controlled, MRI-based, theranostic agent that effectively targets and treats solid tumors via irreversible electroporation while sparing normal tissues, offering a new and promising approach to cancer therapy.

bioengineering↗

bioRxiv2020

In vivo contactless brain stimulation via non-invasive and targeted delivery of magnetoelectric nanoparticles

Non-invasive brain stimulation is valuable for studying neural circuits and treating various neurological disorders in humans. However, the current technologies usually have low spatial and temporal precision and poor brain penetration, which greatly limit their application. A new class of nanoparticles known as magneto-electric nanoparticles (MENs) can be navigated to a targeted brain region with a magnetic field and is highly efficient in converting an externally applied magnetic wave into local electric fields for neuronal activity modulation. Here we developed a new method to fabricate MENs of CoFe2O4-BaTiO3 core-shell structure that had excellent magneto-electrical coupling properties. Using calcium imaging of organotypic and acute cortical slices from GCaMP6s transgenic mice, we demonstrated their efficacy in reliably evoking neuronal responses with a short latency period. For in vivo non-invasive delivery of MENs to brain, fluorescently labeled MENs were intravenously injected and guided to pass through the blood brain barrier to a targeted brain region by applying a magnetic field gradient. A magnetic field ([~]450 Oe at 10 Hz) applied to mouse brain was able to reliably evoke cortical activities, as revealed by in vivo two-photon and mesoscopic imaging of calcium signals at both cellular and global network levels. The effect was further confirmed by the increased number of c-Fos expressing cells after stimulation. Neither brain delivery of MENs nor the subsequent magnetic stimulation caused any significant increases in the numbers of GFAP and IBA1 positive astrocytes and microglia in the brain. This study demonstrates the feasibility of using MENs as a novel efficient and non-invasive technique of contactless deep brain stimulation that may have great potential for translation.

neuroscience↗